Fighting Like a Girl or Boy Determined By Gene in Fruit Flies

Fighting male fruit flies. Image source: Kravitz LabCLICK THE PHOTO to see video of a female fruit fly attacking a female. To see a male attack a male, click here.

BOSTON-November 19, 2006-Fighting like a girl or fighting like a boy is hardwired
into fruit fly neurons, according to a study in the Nov. 19 Nature
Neuroscience advance online publication by a research team from
Harvard Medical School and the Institute of Molecular Pathology in
Vienna.

The results confirm that a gene known as "fruitless" is a key
factor underlying sexual differences in behavior. The findings mark a
milestone in an unlikely new animal model for understanding the
biology of aggression and how the nervous system gives rise to
different behaviors.

"Aggression is a very serious problem in society, and it's a problem
with a biological and genetic component," said co-author Edward
Kravitz, the George Packer Berry professor of neurobiology at HMS,
who developed the fruit fly fighting model used. "We want to
understand that. I can't think of a better system to study than fruit
flies. And no one gets hurt."

The fruitless gene is known for its role in male courtship. The large
gene makes a set of male-specific proteins found exclusively in the
nervous system of fruit flies, in about 2 percent of neurons. The
proteins are necessary for normal courting. Males missing the
proteins do not court females, and they sometimes court males, other
research groups have shown. Females with a male version of the gene
perform the male courting ritual with other females.

The same gene directs another sex-specific behavior -- fighting
patterns, the new study shows. Female fighting, for example, largely
involves head butts and some shoving. Males prefer lunges; they rear
up on their back legs and snap their forelegs down hard - sometimes
nailing an opponent that is slow to retreat.

The flies undergo a major role reversal when the male and female gene
versions are switched. With a feminine fruitless gene, male flies
adopt more ladylike tactics, mostly the head butt and some shoving.
With the masculine fruitless gene, females instinctively lunge to the
exclusion of their usual maneuvers.

The gender-bending fruit flies were first developed to study
courtship in the Austrian lab of co-author Barry Dickson, director of
the Institute of Molecular Pathology. Dickson created male flies with
the female version of the gene and female flies with the male version.

In Dickson's courtship studies, male fruit flies with the female
fruitless gene were not acting like males, but it wasn't clear that
they were acting like females, either. (Ultimately, courtship
behavior is constrained by pheromones and anatomy, which do not
change.) He contacted Kravitz, hoping that aggression studies would
resolve the lingering question of male behavior changes.

Meanwhile, co-author Steven Nilsen, a postdoctoral fellow in
Kravitz's lab, had similar questions and was staging contests between
another line of mutant fruitless flies without such clear
brain-switching genetics. So Austrian postdoctoral fellow Eleftheria
Vrontou, the lead author, packed up their flies and took them to the
Boston fruit fly fight club.

For the past five years, researchers in Kravitz's lab have been
methodically scoring fruit fly fights to determine the normal
aggression patterns with the long-term goal of documenting how genes
and molecules change those patterns. They stage male fights on
bottle-cap-sized food cups decorated with a headless female (a live
female will fly away, leaving males nothing to fight over). Female
flies fight over an extra dab of fresh yeast paste -- their version of
dark chocolate, Kravitz said. The flies are videotaped. The movies
are replayed in slow motion to record each move and countermove.

"Ed has systematically developed reproducibly aggressive behavior in
flies and paved the way for serious analysis," said Laurie Tompkins,
program director at the National Institute of General Medical
Sciences, which funds the work. The fruit fly aggression model is
part of a new trend to use fruit flies as models to study complex
behaviors, including sleep and responses to painful stimuli, Tompkins
said. "Drosophila have marvelous advantages in terms of genetic
tricks," she said, "and flies in many respects behave and respond
similarly to humans."

The findings provide a welcome guidepost to help enable future
research to track down the underlying neural circuitry, said Bruce
Baker, a biology professor at Stanford who first linked the fruitless
gene to male-specific courtship behavior. "That's a pretty big
thing," Baker said. "We can think about understanding in molecular
detail how we go from the initial genes and the proteins they encode
to the nervous system that causes our body to respond in certain
ways." More generally, he said, such studies form a potential bridge
between systems neuroscience studies of behavior and modern molecular
neuroscience research into individual neurons and synapses.